: End-stage renal disease (ESRD) remains a major health problem in the United States and continues to increase annually. By 1997 there were over 300,000 patients enrolled in the Medicare-fund ESRD program for renal replacement therapy, will the total cost of care for ESRD patients in the United States at over $15 billion annually. The goal of this project is to search for a gene (or genes) that confers susceptibility to hypertensive ESRD in a rat model. A region of rat chromosome 1 has previously been identified as harboring a gene for renal failure (termed Rf-1), from a backcross-that has been replicated in an F2 intercross, both derived from the Fawn Hooded Hypertensive (FHH) rat and the normotensive ACI parental strains of rat. Under the proposed project I will search for this gene using a variety of state of the art molecular genetics techniques designed to narrow down the universe of possible disease-causing genes; ultimately the gene will be sequenced in both the disease strain (FHH) and normal strains (ACI, Brown Norway) to identify molecular changes potentially responsible for the susceptibility to hypertensive ESRD. As it is believed that the mechanisms of renal disease onset and progression are the same or similar in humans as in rats, this work may ultimately lead to a better understanding of ESRD in humans.